- Overview
- Retinitis pigmentosa
- Cone/cone-rod dystrophy
- Additional information
- Multimodal imaging
- References
Overview
Gene (OMIM No.) |
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Function of gene/protein |
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Clinical phenotype (OMIM phenotype no.) |
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Inheritance |
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Signs for AD-RP |
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Signs for AR-RP |
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Visual function | Autosomal dominant RP1-retinopathy:
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Systemic features |
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Key investigations |
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Molecular diagnosis | Next generation sequencing
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Management | Ocular |
Therapies under research |
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Further information |
Additional information
Mutations in RP1 cause 3-8% of AD-RP cases.[5-8] Most pathogenic RP1 mutations causing AD-RP are congregated between amino acid residues 500 and 1503 in exon 4 (a mutation hot-spot), where the p.Arg667X in the most common variant.[5,12]
On the other hand, biallelic variants can be situated in exons 2, 3 and 4 (outside of the AD-RP hot-spot). Exons 2 and 3 contain two doublecortin (DCX) domains which mediate the interaction between photoreceptor outer segment discs with axonemal microtubules.[12] A genotype-phenotype relationship can be observed in biallelic RP1 mutations[12]:
- Presence of two truncating (result in the production of a shortened protein) or null alleles cause a severe and early-onset RP phenotype
- Cone-rod dystrophy and MD are associated with the presence of at least one non-deleterious allele (truncating/null)
- Missense variants in the exon 2 DCX region are associated with later-onset disease in all recessive phenotypes (RP, CORD and MD)
Furthermore, significant phenotypic variability is observed in biallelic RP1 variants. For example, patients from different families harbouring the same homozygous p.Asp202Glu variants can display either AR-RP, cone-rod dystrophy or MD phenotypes clinically.[13,14]
Multimodal imaging

References
- Gao J, Cheon K, Nusinowitz S, et al. Progressive photoreceptor degeneration, outer segment dysplasia, and rhodopsin mislocalization in mice with targeted disruption of the retinitis pigmentosa-1 (Rp1) gene. Proc Natl Acad Sci U S A. 2002;99(8):5698-5703
- Liu Q, Lyubarsky A, Skalet JH, Pugh EN, Jr., Pierce EA. RP1 is required for the correct stacking of outer segment discs. Invest Ophthalmol Vis Sci. 2003;44(10):4171-4183
- Liu Q, Zhou J, Daiger SP, et al. Identification and subcellular localization of the RP1 protein in human and mouse photoreceptors. Invest Ophthalmol Vis Sci. 2002;43(1):22-32
- Liu Q, Zuo J, Pierce EA. The retinitis pigmentosa 1 protein is a photoreceptor microtubule-associated protein. J Neurosci. 2004;24(29):6427-6436
- Bowne SJ, Daiger SP, Hims MM, et al. Mutations in the RP1 gene causing autosomal dominant retinitis pigmentosa. Hum Mol Genet. 1999;8(11):2121-2128
- Pierce EA, Quinn T, Meehan T, McGee TL, Berson EL, Dryja TP. Mutations in a gene encoding a new oxygen-regulated photoreceptor protein cause dominant retinitis pigmentosa. Nat Genet. 1999;22(3):248-254
- Berson EL, Grimsby JL, Adams SM, et al. Clinical features and mutations in patients with dominant retinitis pigmentosa-1 (RP1). Invest Ophthalmol Vis Sci. 2001;42(10):2217-2224
- Payne A, Vithana E, Khaliq S, et al. RP1 protein truncating mutations predominate at the RP1 adRP locus. Invest Ophthalmol Vis Sci. 2000;41(13):4069-4073
- Jacobson SG, Cideciyan AV, Iannaccone A, et al. Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2000;41(7):1898-1908
- Gamundi MJ, Hernan I, Martínez-Gimeno M, et al. Three novel and the common Arg677Ter RP1 protein truncating mutations causing autosomal dominant retinitis pigmentosa in a Spanish population. BMC Med Genet. 2006;7:35
- Audo I, Mohand-Saïd S, Dhaenens CM, et al. RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation. Hum Mutat. 2012;33(1):73-80
- Verbakel SK, van Huet RAC, den Hollander AI, et al. Macular Dystrophy and Cone-Rod Dystrophy Caused by Mutations in the RP1 Gene: Extending the RP1 Disease Spectrum. Invest Ophthalmol Vis Sci. 2019;60(4):1192-1203
- Riera M, Abad-Morales V, Navarro R, et al. Expanding the retinal phenotype of RP1: from retinitis pigmentosa to a novel and singular macular dystrophy. Br J Ophthalmol. 2020;104(2):173-181
- Huckfeldt RM, Grigorian F, Place E, et al. Biallelic RP1-associated retinal dystrophies: Expanding the mutational and clinical spectrum. Mol Vis. 2020;26:423-433. Published 2020 Jun 3